Dr. Kathy Gardner is a Neurologist, currently gaining clinical experience with a busy private practice-entered for a 3 year period of "pay back" time to the State of Wyoming in return for a medical education loan. Prior research and laboratory experience included successful genetic linkage study of a spinocerebellar ataxia family performed during several months of her Neurology residency at the University of Utah/Howard Hughes Medical Institute. This prompted a strong interest in further study of neurogenetics, enhanced by a long standing interest in neuromuscular disorders. During private practice time she characterized and collected DNA samples on several families with inherited neurologic disorders including a very large autosomal dominant family with hemiplegic migraine. Forty five members of this family have been ascertained, clinically examined, and blood lymphocytes transformed by the applicant. The proposed laboratory research focuses on identification of the molecular basis of hemiplegic migraine under the guidance of Dr. Eric Hoffman. During the laboratory research, didactic classes will be pursued equivalent to those taken by PhD candidates in the Department of Molecular Genetics and Biochemistry, supplemented with medical genetics coursework through the Department of Human Genetics. To further her specialized medical training, Dr. Gardner will spend 10% of her time with a headache clinic at the University of Pittsburgh under the mentorship of the Chairman of Neurology, Dr. Roger Simon. The proposed laboratory research will include: linkage analysis of the 45 member hemiplegic migraine family using chromosome l9p. If the family shows linkage to l9p, then the critical region will be genetically defined, a physical map obtained from microsatellite STSs, and candidate and novel cDNAs investigated for mutations. If the family is not linked to l9p, then a genome wide search will be done using microsatellite markers and an "affected only" approach to minimize problems of disease penetrance. Identification of the responsible gene and gene product will possibly allow initiation of clinical trials based on pathophysiology. Learning the molecular genetic techniques necessary to accomplish these goals while continuing to work and relate these findings to clinical problems will provide a strong beginning for an academic career.